TY  - JOUR
AU  - Jovanović Stojanov, Sofija
AU  - Ntungwe, Epole N.
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Pajović, Milica
AU  - Rijo, Patrícia
AU  - Pešić, Milica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6027
AB  - Multidrug resistance in cancer is often mediated by P-glycoprotein. Natural compounds
have been suggested as a fourth generation of P-glycoprotein inhibitors. Coleon U, isolated from
Plectranthus mutabilis Codd., was reported to modulate P-glycoprotein activity but the underlying
mechanism has not yet been revealed. Therefore, the effects of Coleon U on cell viability, proliferation, and cell death induction were studied in a non-small-cell lung carcinoma model comprising
sensitive and multidrug-resistant cells with P-glycoprotein overexpression. P-glycoprotein activity
and mitochondrial membrane potential were assessed by flow cytometry upon Coleon U, sodiumorthovanadate (an ATPase inhibitor), and verapamil (an ATPase stimulator) treatments. SwissADME
was used to identify the pharmacokinetic properties of Coleon U, while P-glycoprotein expression
was studied by immunofluorescence. Our results showed that Coleon U is not a P-glycoprotein
substrate and is equally efficient in sensitive and multidrug-resistant cancer cells. A decrease in
P-glycoprotein activity observed with Coleon U and verapamil after 72 h is antagonized in combination with sodium-orthovanadate. Coleon U induced a pronounced effect on mitochondrial membrane
depolarization and showed a tendency to decrease P-glycoprotein expression. In conclusion, Coleon
U-delayed effect on the decrease in P-glycoprotein activity is due to P-glycoprotein’s functioning
dependence on ATP production in mitochondria.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition
IS  - 7
VL  - 15
DO  - 10.3390/pharmaceutics15071942
SP  - 1942
ER  - 

@article{
author = "Jovanović Stojanov, Sofija and Ntungwe, Epole N. and Dinić, Jelena and Podolski-Renić, Ana and Pajović, Milica and Rijo, Patrícia and Pešić, Milica",
year = "2023",
abstract = "Multidrug resistance in cancer is often mediated by P-glycoprotein. Natural compounds
have been suggested as a fourth generation of P-glycoprotein inhibitors. Coleon U, isolated from
Plectranthus mutabilis Codd., was reported to modulate P-glycoprotein activity but the underlying
mechanism has not yet been revealed. Therefore, the effects of Coleon U on cell viability, proliferation, and cell death induction were studied in a non-small-cell lung carcinoma model comprising
sensitive and multidrug-resistant cells with P-glycoprotein overexpression. P-glycoprotein activity
and mitochondrial membrane potential were assessed by flow cytometry upon Coleon U, sodiumorthovanadate (an ATPase inhibitor), and verapamil (an ATPase stimulator) treatments. SwissADME
was used to identify the pharmacokinetic properties of Coleon U, while P-glycoprotein expression
was studied by immunofluorescence. Our results showed that Coleon U is not a P-glycoprotein
substrate and is equally efficient in sensitive and multidrug-resistant cancer cells. A decrease in
P-glycoprotein activity observed with Coleon U and verapamil after 72 h is antagonized in combination with sodium-orthovanadate. Coleon U induced a pronounced effect on mitochondrial membrane
depolarization and showed a tendency to decrease P-glycoprotein expression. In conclusion, Coleon
U-delayed effect on the decrease in P-glycoprotein activity is due to P-glycoprotein’s functioning
dependence on ATP production in mitochondria.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition",
number = "7",
volume = "15",
doi = "10.3390/pharmaceutics15071942",
pages = "1942"
}

Jovanović Stojanov, S., Ntungwe, E. N., Dinić, J., Podolski-Renić, A., Pajović, M., Rijo, P.,& Pešić, M.. (2023). Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition. in Pharmaceutics
Basel: MDPI., 15(7), 1942.
https://doi.org/10.3390/pharmaceutics15071942

Jovanović Stojanov S, Ntungwe EN, Dinić J, Podolski-Renić A, Pajović M, Rijo P, Pešić M. Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition. in Pharmaceutics. 2023;15(7):1942.
doi:10.3390/pharmaceutics15071942 .

Jovanović Stojanov, Sofija, Ntungwe, Epole N., Dinić, Jelena, Podolski-Renić, Ana, Pajović, Milica, Rijo, Patrícia, Pešić, Milica, "Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition" in Pharmaceutics, 15, no. 7 (2023):1942,
https://doi.org/10.3390/pharmaceutics15071942 . .

TY  - JOUR
AU  - Ntungwe, Epole N.
AU  - Jovanović Stojanov, Sofija
AU  - Duarte, Noélia M.
AU  - Candeias, Nuno R.
AU  - Díaz-Lanza, Ana M.
AU  - Vágvölgyi, Máté
AU  - Hunyadi, Attila
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2022
UR  - https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00711
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9014510
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4945
AB  - In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.
T2  - ACS Medicinal Chemistry Letters
T1  - C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.
IS  - 4
VL  - 13
DO  - 10.1021/acsmedchemlett.1c00711
SP  - 674
EP  - 680
ER  - 

@article{
author = "Ntungwe, Epole N. and Jovanović Stojanov, Sofija and Duarte, Noélia M. and Candeias, Nuno R. and Díaz-Lanza, Ana M. and Vágvölgyi, Máté and Hunyadi, Attila and Pešić, Milica and Rijo, Patrícia",
year = "2022",
abstract = "In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.",
journal = "ACS Medicinal Chemistry Letters",
title = "C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.",
number = "4",
volume = "13",
doi = "10.1021/acsmedchemlett.1c00711",
pages = "674-680"
}

Ntungwe, E. N., Jovanović Stojanov, S., Duarte, N. M., Candeias, N. R., Díaz-Lanza, A. M., Vágvölgyi, M., Hunyadi, A., Pešić, M.,& Rijo, P.. (2022). C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.. in ACS Medicinal Chemistry Letters, 13(4), 674-680.
https://doi.org/10.1021/acsmedchemlett.1c00711

Ntungwe EN, Jovanović Stojanov S, Duarte NM, Candeias NR, Díaz-Lanza AM, Vágvölgyi M, Hunyadi A, Pešić M, Rijo P. C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.. in ACS Medicinal Chemistry Letters. 2022;13(4):674-680.
doi:10.1021/acsmedchemlett.1c00711 .

Ntungwe, Epole N., Jovanović Stojanov, Sofija, Duarte, Noélia M., Candeias, Nuno R., Díaz-Lanza, Ana M., Vágvölgyi, Máté, Hunyadi, Attila, Pešić, Milica, Rijo, Patrícia, "C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators." in ACS Medicinal Chemistry Letters, 13, no. 4 (2022):674-680,
https://doi.org/10.1021/acsmedchemlett.1c00711 . .